Bibliographic Details
| Title: |
Gankyrin Activates IL-8 to Promote Hepatic Metastasis of Colorectal Cancer. |
| Authors: |
Zhaofang Bai1, Yanhong Tai2, Weihua Li3, Cheng Zhen1, Weiting Gu3, Zhao Jian1, Qianyi Wang1, Lin, Jieru E.4, Qing Zhao1, Weili Gong1, Bing Liang1, Chenguang Wang3 Chenguang.Wang@jefferson.edu, Tao Zhou1 tzhou@ncba.ac.cn |
| Source: |
Cancer Research. Jul2013, Vol. 73 Issue 14, p4548-4558. 11p. |
| Subject Terms: |
*LIVER metastasis, *METASTASIS, *COLON cancer, *INTERLEUKIN-1, *GENOMES |
| Abstract: |
Hepatic metastasis is responsible for the majority of colorectal cancer (CRC)-related mortalities. Although Gankyrin (PSMD10) has been implicated in cancer metastasis, its exact role and underlying mechanisms of CRC hepatic metastasis remain largely unknown. Herein, we showed that the expression of Gankyrin was higher in primary CRC with hepatic metastasis compared with CRC without metastasis. RNAi-mediated silencing of Gankyrin expression in highly metastatic human CRC cells impaired their migratory and metastatic capacity in vivo. Genome-wide transcriptome profiling revealed activation of the interleukin (IL)-8 signaling pathway by Gankyrin. Protein levels of IL-8 and cyclin D1 (CCND1), the two important molecules in the IL-8 pathway, were positively correlated with Gankyrin expression in human CRC specimens. Furthermore, genetic deletion of cyclin D1 showed its requirement in Gankyrin-mediated cell migration. Finally, administration of recombinant IL-8 rescued the migratory defect of CRC cells where Gankyrin expression was silenced. Together, our findings highlight the importance of Gankyrin in hepatic metastasis of CRC and point out its candidature as a potential prognostic marker and therapeutic target to improve the clinical management of metastatic CRC. [ABSTRACT FROM AUTHOR] |
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| Database: |
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